CN104326977A - Preparation method of 6,7-diethyl-4-hydroxyquinoline - Google Patents
Preparation method of 6,7-diethyl-4-hydroxyquinoline Download PDFInfo
- Publication number
- CN104326977A CN104326977A CN201410548283.3A CN201410548283A CN104326977A CN 104326977 A CN104326977 A CN 104326977A CN 201410548283 A CN201410548283 A CN 201410548283A CN 104326977 A CN104326977 A CN 104326977A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- ring closure
- xylol
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
Abstract
The invention discloses a preparation method of 6,7-diethyl-4-hydroxyquinoline, which takes 1-(3,4-diethyl-phenyl)butanone as an initial raw material, and is performed with steps of nitrification, reduction and ring closure to obtain a target product, and the compound is an important drug intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, particularly a kind of preparation method of 6,7-diethyl-4-hydroxyquinoline.
Technical background
Compound 6,7-diethyl-4-hydroxyquinoline, structural formula is:
This compound 6,7-diethyl-4-hydroxyquinoline and relevant derivative have widespread use in pharmaceutical chemistry and organic synthesis.The synthesis of current 6,7-diethyl-4-hydroxyquinolines is comparatively difficult.Therefore, need exploitation raw material to be easy to get, easy to operate, reaction is easy to control, the synthetic method that overall yield is suitable.
Summary of the invention
The invention discloses the method that one prepares 6,7-diethyl-4-hydroxyquinoline, with 1-(3,4-diethyl phenyl) ethyl ketone for starting raw material, obtain target product 4 through nitrated, reduction, Guan Huan, synthetic route as shown in Figure 1.Synthesis step is as follows:
(1) for starting raw material, 2 are obtained through nitration reaction with 1-(3,4-diethyl phenyl) ethyl ketone;
(2) carry out reduction reaction 2, obtain 3;
(3) carry out ring closure reaction 3 and obtain 4;
One preferred embodiment in, the reagent that described nitration reaction prepares compound 2 used is selected from concentrated nitric acid; Described reduction reaction is prepared compound 3 reductive agent used and is selected from palladium carbon-hydrogen; The alkali that described ring closure reaction prepares compound 4 used is selected from sodium.
One preferred embodiment in, the solvent that described nitration reaction prepares compound 2 used is selected from acetic acid; Described reduction reaction prepares compound 3 solvent selected from methanol used; Described ring closure reaction prepares compound 4 solvent selected from ethanol used.
One preferred embodiment in, it is room temperature that described ring closure reaction prepares compound 2 temperature of reaction used; It is room temperature that described reduction reaction prepares compound 3 temperature used; Described ring closure reaction prepare compound 4 used be the reflux temperature of solvent.
The present invention relates to a kind of preparation method of 6,7-diethyl-4-hydroxyquinoline, there is no other Patents bibliographical informations at present.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 6,7-diethyl-4-hydroxyquinoline.
The present invention is further described by the following embodiment, and these descriptions are not be further limited content of the present invention.One skilled in the art will understand that the equivalent replacement that technical characteristic of the present invention is done, or improve accordingly, still belong within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 1-(4,5-diethyl-2-nitrophenyl) ethyl ketone
29g 1-(3,4-diethyl phenyl) ethyl ketone joins in 260ml acetic acid, add 62g concentrated nitric acid, stirred overnight at room temperature, concentrate and add ethyl acetate and water again, separatory, drying, concentrated, residuum upper prop is separated and obtains 31g 1-(4,5-diethyl-2-nitrophenyl) ethyl ketone.
(2) synthesis of 1-(amino-4, the 5-diethyl phenyl of 2-) ethyl ketone
30g 1-(4,5-diethyl-2-nitrophenyl) ethyl ketone is joined in 240ml anhydrous methanol, then adds 4g 10% palladium carbon, pass into hydrogen, stirring at room temperature 4 hours, filter, collect filtrate, concentrate to obtain 22g 1-(amino-4, the 5-diethyl phenyl of 2-) ethyl ketone.
The synthesis of (3) 6,7-diethyl-4-hydroxyquinolines
12g sodium is joined in 230ml dehydrated alcohol, 20g (7-methyl-imidazoles also [1 again, 2-a] pyridine-2-base) methyl alcohol and 32g ethyl formate, reflux stirs 9 hours, concentrated, adds ethyl acetate and the aqueous solution, extraction separatory, dry, concentrated, on residuum, silicagel column is separated to obtain 8g 6,7-diethyl-4-hydroxyquinoline.
Claims (6)
1. the preparation method of a diethyl-4-hydroxyquinoline, with 1-(3,4-diethyl phenyl) ethyl ketone for starting raw material, obtain target product 4 through nitrated, reduction, Guan Huan, synthetic route is as follows.
2. method according to claim 1, it is characterized by 3 described step reactions is,
(1) for starting raw material, 2 are obtained through nitration reaction with 1-(3,4-diethyl phenyl) ethyl ketone;
(2) carry out reduction reaction 2, obtain 3;
(3) carry out ring closure reaction 3 and obtain 4;
3. according to the method for claim 1-2, it is characterized in that, described nitration reaction is prepared compound 2 reagent used and is selected from one or both mixture in concentrated nitric acid, nitrosonitric acid; Described reduction reaction is prepared compound 3 reductive agent used and is selected from the mixture of one or more in sodium borohydride, POTASSIUM BOROHYDRIDE, lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine, iron powder, zinc powder, palladium carbon-hydrogen; Described ring closure reaction is prepared compound 4 alkali used and is selected from the mixture of one or more in sodium, sodium hydrogen, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, salt of wormwood, triethylamine, sodium bicarbonate, pyridine, triisopropylamine, saleratus.
4. according to the method for claim 1-2, it is characterized in that, described nitration reaction prepares compound 2 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, acetic acid, chloroform; Described reduction reaction prepares compound 3 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide, water; Described ring closure reaction prepares compound 4 solvent selected from methanol used, ethanol, n-propyl alcohol, Virahol, tetrahydrofuran (THF), methylene dichloride, toluene, o-Xylol, p-Xylol, m-xylene, N, the mixture of one or more in dinethylformamide, N,N-dimethylacetamide.
5. according to the method for claim 1-2, it is characterized in that, described nitration reaction prepares the reflux temperature that compound 2 temperature of reaction used is 0 DEG C ~ solvent; Described reduction reaction prepares the reflux temperature that compound 3 temperature used is 0 DEG C ~ solvent; Described ring closure reaction prepare compound 4 used be the reflux temperature of 0 DEG C ~ solvent.
6. according to the method for claim 1-2, it is characterized in that, it is room temperature that described ring closure reaction prepares compound 2 temperature of reaction used; It is room temperature that described reduction reaction prepares compound 3 temperature used; Described ring closure reaction prepare compound 4 used be the reflux temperature of solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410548283.3A CN104326977A (en) | 2014-10-15 | 2014-10-15 | Preparation method of 6,7-diethyl-4-hydroxyquinoline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410548283.3A CN104326977A (en) | 2014-10-15 | 2014-10-15 | Preparation method of 6,7-diethyl-4-hydroxyquinoline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104326977A true CN104326977A (en) | 2015-02-04 |
Family
ID=52401800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410548283.3A Pending CN104326977A (en) | 2014-10-15 | 2014-10-15 | Preparation method of 6,7-diethyl-4-hydroxyquinoline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104326977A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749006A (en) * | 2017-01-09 | 2017-05-31 | 湖南华腾制药有限公司 | It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 |
| CN107286090A (en) * | 2016-04-05 | 2017-10-24 | 湖南华腾制药有限公司 | A kind of preparation method of 6,7- dimethyl -4- oxyquinolines |
| CN107698504A (en) * | 2016-08-09 | 2018-02-16 | 湖南华腾制药有限公司 | A kind of preparation method of the oxyquinoline of 6 chlorine, 7 ethyl 4 |
-
2014
- 2014-10-15 CN CN201410548283.3A patent/CN104326977A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107286090A (en) * | 2016-04-05 | 2017-10-24 | 湖南华腾制药有限公司 | A kind of preparation method of 6,7- dimethyl -4- oxyquinolines |
| CN107698504A (en) * | 2016-08-09 | 2018-02-16 | 湖南华腾制药有限公司 | A kind of preparation method of the oxyquinoline of 6 chlorine, 7 ethyl 4 |
| CN106749006A (en) * | 2017-01-09 | 2017-05-31 | 湖南华腾制药有限公司 | It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104262257A (en) | Preparation method of pyrazole derivative | |
| CN104230853B (en) | A kind of preparation method of (p-methylphenyl) methylamine-N-ethylmorpholine hydrochloride | |
| CN104292145A (en) | Preparation method of 6-bromoindole derivative | |
| CN104292179A (en) | Preparation method of 2-chlorobenzo[d]oxazole-5-formaldehyde | |
| CN104926775A (en) | Preparation method of fluorine-containing pyran derivative | |
| CN104277042A (en) | Preparation method of imidazopyridine derivative | |
| CN104326977A (en) | Preparation method of 6,7-diethyl-4-hydroxyquinoline | |
| CN104387367A (en) | Method for preparing disubstituted benzimidazole derivative | |
| CN104829581A (en) | Preparation method of 6-bromo pyran derivative | |
| CN104829574A (en) | 8-bromo pyran derivative preparation method | |
| CN104844549A (en) | Preparation method of 7 - bromine pyran derivatives | |
| CN104829576A (en) | Preparation method of 7-fluoropyran derivatives | |
| CN104829575A (en) | Preparation method of 6-fluoropyran derivative | |
| CN104292143A (en) | 2-(4-bromine benzyl) pyrrolidine preparation method | |
| CN104402880A (en) | Preparation method of imidazopyridine derivative | |
| CN103739545B (en) | Simple preparation method of vitamin B6 | |
| CN105001118A (en) | Method for preparing iodine-containing azido compound | |
| CN105001117A (en) | Method for synthesizing chlorine-containing azide compound | |
| CN104628721A (en) | Preparation method of imidazo [1, 2-a] pyridine derivative | |
| CN105061253A (en) | Preparation method of bromine-containing azide | |
| CN104262265B (en) | A kind of preparation method of tetrahydro quinazoline derivative | |
| CN105130841A (en) | Preparation method of 3-iodophenyl azide compound | |
| CN105061254A (en) | Synthetic method of bromine-containing azide | |
| CN104370835A (en) | Preparation method of triazole derivative | |
| CN104341344A (en) | Preparation method of 3-(2-methylquinoline-6-yl) propionamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150204 |